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Revised: 04/06/2006

DIAGNOSTIC IMMUNOLOGY - SYPHILIS SEROLOGY

This College of American Pathologists (CAP) Laboratory Accreditation Program (LAP) Checklist is provided as a Microsoft® Word 2000 electronic file for convenience and for educational purposes. It represents the fully-approved version for use in the LAP as of the date given in the header.

Newer approved versions of this Checklist may be found via the Internet at the CAP Web site (http://www.cap.org/apps/docs/laboratory_accreditation/checklists/checklistftp.html) for both viewing and download to your computer.

If you are currently enrolled in the CAP LAP and are preparing for an inspection, please note:

The Checklists undergo frequent revision, and the contents may have changed after you receive your inspection packet. If a Checklist has been updated since receiving your packet, you will be inspected based upon the Checklists that were mailed to you in your application or reapplication packet.

For questions about the use of Checklists in the inspection process, please e-mail the CAP at [email protected], or call (800) 323-4040, ext. 6065. Suggestions for content improvement should be sent by e-mail to LAP at [email protected].

All checklists are © 2006 College of American Pathologists. All rights reserved.

http://www.cap.org/apps/docs/laboratory_accreditation/checklists/checklistftp.html

College of American Pathologists Revised: 04/06/2006

OUTLINE

SUMMARY OF CHANGESINSPECTION TECHNIQUES – KEY POINTSLABORATORY SAFETYPROFICIENCY TESTINGQUALITY MANAGEMENT AND QUALITY CONTROL

GENERAL ISSUESPROCEDURE MANUALSPECIMEN COLLECTION AND HANDLINGRESULTS REPORTINGREAGENTSCALIBRATION AND STANDARDSCONTROLSINSTRUMENTS AND EQUIPMENT

Analytic BalancesPROCEDURES AND TEST SYSTEMS

BLOOD TYPE, GROUP, AND/OR ANTIBODY SCREENSSYPHILIS SEROLOGY

PERSONNELPHYSICAL FACILITIES

DIAGNOSTIC IMMUNOLOGY - SYPHILIS SEROLOGY of 55


SUMMARY OF CHANGESDIAGNOSTIC IMMUNOLOGY - SYPHILIS SEROLOGY Checklist

4/6/2006 Edition

The following questions have been added, revised, or deleted in this edition of the checklist, or in the two editions immediately previous to this one.

If this checklist was created for a reapplication, on-site inspection or self-evaluation it has been customized based on the laboratory's activity menu. The listing below is comprehensive; therefore some of the questions included may not appear in the customized checklist. Such questions are not applicable to the testing performed by the laboratory.

Note: For revised checklist questions, a comparison of the previous and current text may be found on the CAP website. Click on Laboratory Accreditation, Checklists, and then click the column marked Changes for the particular checklist of interest.

NEW Checklist Questions

Question Effective Date IMM.16466 04/06/2006IMM.22732 04/06/2006IMM.33374 04/06/2006IMM.33448 04/06/2006IMM.33522 04/06/2006IMM.33596 04/06/2006IMM.33670 04/06/2006IMM.33744 04/06/2006IMM.33892 04/06/2006IMM.33966 04/06/2006IMM.34362 04/06/2006IMM.35075 04/06/2006IMM.35241 04/06/2006IMM.40755 04/06/2006IMM.40790 04/06/2006IMM.40825 04/06/2006

REVISED Checklist Questions

Question Effective Date IMM.31000 04/06/2006IMM.33818 04/06/2006IMM.34140 04/06/2006IMM.34250 04/06/2006IMM.34450 04/06/2006IMM.38078 04/06/2006



IMM.41400 04/06/2006

DELETED Checklist Questions

Question Effective Date IMM.30200 04/06/2006IMM.30250 04/06/2006IMM.32170 04/06/2006IMM.34160 04/06/2006IMM.34200 04/06/2006IMM.61100 10/06/2005IMM.70000 12/29/2004



The checklists used in connection with the inspection of laboratories by the Commission on Laboratory Accreditation (“CLA”) of the College of American Pathologists have been created by the College and are copyrighted works of the College. The College has authorized copying and use of the checklists by College inspectors in conducting laboratory inspections for the CLA and by laboratories that are preparing for such inspections. Except as permitted by section 107 of the Copyright Act, 17 U.S.C. sec. 107, any other use of the checklists constitutes infringement of the College’s copyrights in the checklists. The College will take appropriate legal action to protect these copyrights.

IMPORTANT: The contents of the Laboratory General Checklist are applicable to the Immunology section of the laboratory.

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INSPECTION TECHNIQUES – KEY POINTS

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I. READ – OBSERVE – ASK – the three methods of eliciting information during the inspection process. These three methods may be used throughout the day in no particular order. Plan the inspection in a way that allows adequate time for all three components.

READ = Review of Records and DocumentsDocument review verifies that procedures and manuals are complete, current, available to staff, accurate and reviewed, and describe good laboratory practice. Make notes of any questions you may have, or processes you would like to observe as you read the documentation.

OBSERVE – ASK = Direct Observation and Asking QuestionsObserving and asking questions accomplish the following:

1. Verifies that the actual practice matches the written policy or procedure2. Ensures that the laboratory processes are appropriate for the testing performed3. Ensures that outcomes for any problem areas, such as PT failures and issues/problems

identified through the quality management process, have been adequately investigated and resolved

4. Ensures that previously cited deficiencies have been corrected

Use the following techniques: Observe laboratory practices – look at what the laboratory is actually doing. Compare the

written policy/procedure to what you actually observe in the laboratory to ensure the written policy/procedure accurately reflects laboratory practice. Note if practice deviates from the documented policies/procedures.

Ask open ended, probing questions – these are starting points that will allow you to obtain large amounts of information, and help you clarify your understanding of the documentation you’ve seen



and observations you’ve made. This eliminates the need to ask every single checklist question, as the dialogue between you and the laboratory may address multiple checklist questions.

Ask open-ended questions that start with phrases such as “show me how…” or “tell me about …” or “what would you do if…”. By asking questions that are open-ended, or by posing a hypothetical problem, you will avoid “cookbook” answers. For example, ask “Could you show me the specimen transport policy and show me how you ensure optimum specimen quality?” This will help you to determine how well the technical staff is trained, whether or not they are adhering to the lab’s procedures and policies, and give you a feel for the general level of performance of the laboratory.

Ask follow-up questions for clarification. Generally, it is best not to ask the checklist questions verbatim. For example, instead of asking the checklist question “Is there documentation of corrective action when control results exceed defined tolerance limits?” ask, “What would you do if the SD or CV doubles one month?” A follow-up probing question could be, “What would you do if you were unable to find a cause for the change in SD or CV?”

II. Evaluate Selected Specimens and Tests in Detail

For the Laboratory General Checklist: Follow a specimen through the laboratory. By following a specimen from collection to test result, you can cover multiple checklist questions in the Laboratory General checklist: questions on the specimen collection manual; phlebotomy; verbal orders; identification of patients and specimens; accessioning; and result reporting, including appropriate reference ranges, retention of test records, maintaining confidentiality of patient data, and proper handling of critical values and revisions to reports.

For the individual laboratory sections: Consult the laboratory’s activity menu and focus on tests that potentially have the greatest impact on patient care. Examples of such tests include HIV antibodies, hepatitis B surface antigen, urine drugs of abuse, quantitative beta-hCG, cultures of blood or CSF, acid-fast cultures, prothrombin time and INR reporting, and compatibility testing and unexpected antibody detection. Other potentially high-impact tests may be identified by looking at very high or low volume tests in the particular laboratory, or problems identified by reviewing the Variant Proficiency Testing Performance Report.

To evaluate preanalytic and postanalytic issues: Choose a representative specimen and “follow" the specimen through the laboratory or section of the laboratory, reviewing appropriate records in the preanalytic and postanalytic categories.

To evaluate analytic processes: Choose 2 or 3 analytes and perform a comprehensive review of records, including procedure manuals, quality control and proficiency testing records, instrument maintenance records and method performance validations for the last 2 years, selecting timeframes at the beginning, mid-point, and end of this timeframe. Compare instrument print-outs to patient reports and proficiency testing results to ensure accurate data entry. If problems are identified, choose additional tests or months to review.



III. Verify that proficiency testing problem have been resolved: From the inspector’s packet, review the Variant PT Performance Report that identifies, by analyte, all of the PT scores below 100%. Correlate any PT problems to QC or maintenance records from the same time period. Be thorough when reviewing these representative records, selecting data from the beginning, middle and end of the period since the last on-site inspection.

IV. Review correction of previous deficiencies: Review the list of deficiencies from the previous on-site inspection provided in the inspector’s packet. Ensure that they have been appropriately addressed.

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LABORATORY SAFETY

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The inspector should review relevant questions from the Safety section of the Laboratory General checklist, to assure that the diagnostic immunology – syphilis serology laboratory is in compliance. Please elaborate upon the location and the details of each deficiency in the Inspector's Summation Report.

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PROFICIENCY TESTING

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IMM.10000 Phase II N/A YES NO

Is the laboratory enrolled in the appropriate required CAP Surveys or CAP-approved alternative proficiency testing (PT) program for the patient/client testing performed?

NOTE: The list of analytes for which CAP requires proficiency testing is available on the CAP website [http://www.cap.org/apps/docs/laboratory_accreditation/checklists/checklist_reference_links.doc] or by phoning 800-323-4040 (or 847-832-7000), option 1. The laboratory’s participation in proficiency testing must include all analytes on this list for which it performs patient testing. Participation in proficiency testing may be through CAP Surveys or a CAP-approved proficiency testing provider. Laboratories will not be penalized if they are unable to enroll in an oversubscribed program. If unable to enroll, however, the laboratory must implement an alternative assessment procedure for the affected analytes. For regulated analytes, if the CAP and CAP-approved alternative PT programs are oversubscribed, CMS requires the laboratory to attempt to enroll in another CMS-approved PT program.

COMMENTARY:


http://www.cap.org/apps/docs/laboratory_accreditation/checklists/checklist_reference_links.doc

http://www.cap.org/apps/docs/laboratory_accreditation/checklists/checklist_reference_links.doc


N/A

REFERENCES: 1) Department of Health and Human Services, Centers for Medicare and Medicaid Services. Clinical laboratory improvement amendments of 1988; final rule. Fed Register. 2003(Jan 24):7146 [42CFR493.801]; 2) Westgard JO, et al. Laboratory precision performance. State of the art versus operating specifications that assure the analytical quality required by clinical laboratory improvement amendments proficiency testing. Arch Pathol Lab Med. 1996;120:621-625; 3) NCCLS. Continuous quality management: essential management approaches and their use in proficiency testing; proposed guideline GP22-P. Wayne, PA: NCCLS, 1997; 4) College of American Pathologists, Commission on Laboratory Accreditation. Standards for laboratory accreditation; standard III. Northfield, IL: CAP, 1998.


For tests for which CAP does not require PT, does the laboratory at least semiannually 1) participate in external PT, or 2) exercise an alternative performance assessment system for determining the reliability of analytic testing?

NOTE: Appropriate alternative performance assessment procedures may include: split sample analysis with reference or other laboratories, split samples with an established in-house method, assayed material, regional pools, clinical validation by chart review, or other suitable and documented means. It is the responsibility of the laboratory director to define such alternative performance assessment procedures, as applicable, in accordance with good clinical and scientific laboratory practice. Participation in ungraded/educational proficiency testing programs also satisfies this checklist question.

COMMENTARY:

N/A

REFERENCE: Department of Health and Human Services, Centers for Medicare and Medicaid Services. Clinical laboratory improvement amendments of 1988; final rule. Fed Register. 2003(Jan 24):7184 [42CFR493.1236(c)(1)].


Does the laboratory integrate all proficiency survey samples into the routine laboratory workload as much as possible, and are those samples analyzed by personnel who routinely test patient samples, using the same primary method systems as for patient samples?

NOTE: Replicate analysis of samples is acceptable only if patient specimens are routinely analyzed in the same manner. If the laboratory uses multiple methods for an analyte, proficiency testing samples should be analyzed by the primary method. There must not be any interlaboratory communication of proficiency testing data before results reporting. The educational purposes of proficiency testing are



best served by a rotation that allows all technologists to be involved in the proficiency testing program. Records of these studies must be kept and can be an important part of the competency and continuing education documentation in the personnel files of the individuals. When external proficiency testing materials are not available, the semi-annual alternative performance assessment process should also be integrated within the routine workload.

COMMENTARY:

N/A

REFERENCES: 1) Department of Health and Human Services, Centers for Medicare and Medicaid Services. Clinical laboratory improvement amendments of 1988; final rule. Fed Register. 2003(Jan 24):7146 [42CFR493.801(b)]; 2) Shahangian S, et al. Toward optimal PT use. Med Lab Observ. 2000;32(4):32-43.


Is there evidence of evaluation and, if indicated, corrective action taken in response to "unacceptable" results on the proficiency testing reports and results of the alternative performance assessment system?

NOTE: The evaluation must document the specific reason(s) for the "unacceptable" result(s) and actions taken to reduce the likelihood of recurrence. This must be done within one month after the laboratory receives its proficiency testing evaluation. Also, the laboratory must review its results, and institute corrective action as appropriate, for challenges that were intended to be graded, but for which no grade was received (for example, because the laboratory did not submit its results, used the incorrect method code, or because of lack of consensus).

COMMENTARY:

N/A

REFERENCE: Department of Health and Human Services, Centers for Medicare and Medicaid Services. Clinical laboratory improvement amendments of 1988; final rule. Fed Register. 2003(Jan 24):7173 [42CFR493.1407(e)(4)(iv)].


Is there documented evidence of ongoing evaluation by the laboratory director or designee of the proficiency testing and alternative performance assessment results?

COMMENTARY:



There must be evidence of ongoing evaluation by the laboratory director or designee of proficiency testing and alternative performance assessment results.

REFERENCES: 1) Department of Health and Human Services, Centers for Medicare and Medicaid Services. Clinical laboratory improvement amendments of 1988; final rule. Fed Register. 2003(Jan 24):7173 [42CFR493.1407(e)(4)(iii)]; 2) Cembrowski GS, et al. The detection of problem analytes in a single proficiency test challenge in the absence of the Centers for Medicare and Medicaid Services rule violations. Arch Pathol Lab Med. 1993;117:437-443; 3) NCCLS. Using proficiency testing (PT) to improve the clinical laboratory; approved guideline GP27-A. Wayne, PA: NCCLS, 1998.

**NEW** 04/06/2006


Is there a policy that prohibits interlaboratory communication about proficiency testing samples until after the deadline for submission of data to the proficiency testing provider?

COMMENTARY:

N/A

REFERENCES: 1) Department of Health and Human Services, Centers for Medicare and Medicaid Services. Clinical laboratory improvement amendments of 1988; final rule. Fed Register. 1992(Feb 28):7146 [42CFR493.801(b)(3)]; 2) Bierig JR. Comparing PT results can put a lab’s CLIA license on the line. Northfield, IL: College of American Pathologists CAP Today. 2002;16(2):84-87.

**NEW** 04/06/2006


Is there a policy that prohibits referral of proficiency testing specimens to another laboratory?

NOTE: Under CLIA-88 regulations, there is a strict prohibition against referring proficiency testing specimens to another laboratory. In other words, the laboratory may not refer a proficiency testing specimen to a laboratory with a different CLIA number (even if the second laboratory is in the same health care system).

COMMENTARY:

N/A

REFERENCE: Department of Health and Human Services, Centers for Medicare & Medicaid Services. Clinical laboratory improvement amendments of 1988; final rule. Fed Register. 1992(Feb 28): [42CFR493.801(b)(4)].



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QUALITY MANAGEMENT AND QUALITY CONTROL

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GENERAL ISSUES

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Does the immunology laboratory have a written quality management/quality control (QM/QC) program?

NOTE: The QM/QC program in the immunology laboratory must be clearly defined and documented. The program must ensure quality throughout the preanalytic, analytic, and post-analytic (reporting) phases of testing, including patient identification and preparation; specimen collection, identification, preservation, transportation, and processing; and accurate, timely result reporting. The program must be capable of detecting problems in the laboratory’s systems, and identifying opportunities for system improvement. The laboratory must be able to develop plans of corrective/preventive action based on data from its QM system.

All QM questions in the Laboratory General Checklist pertain to the immunology laboratory.

COMMENTARY:

N/A


Is there a documented procedure describing methods for patient identification, patient preparation, specimen collection and labeling, specimen preservation, and conditions for transportation, and storage before testing, consistent with good laboratory practice?

COMMENTARY:

N/A




Is there evidence of ongoing evaluation of instrument function and maintenance, temperature, etc.?

COMMENTARY:

N/A


Is there documentation of corrective action taken when values for instrument function, temperature, etc., exceed defined tolerance limits?

COMMENTARY:

N/A


For numeric QC data, are statistics (such as S.D. and C.V.) calculated at specified intervals to define analytic precision?

COMMENTARY:

N/A

REFERENCES: 1) Mukherjee KL. Introductory mathematics for the clinical laboratory. Chicago, IL: American Society of Clinical Pathology, 1979:81-94; 2) Barnett RN. Clinical laboratory statistics. 2nd ed. Boston, MA: Little, Brown, 1979; 3) Weisbrodt IM. Statistics for the clinical laboratory. Philadelphia, PA: JB Lippincott, 1985; 4) Matthews DF, Farewell VT. Understanding and using medical statistics. New York, NY: Karger, 1988.


Does the laboratory have an action protocol when data from precision statistics change significantly from previous data?

COMMENTARY:

N/A




Is there a documented system in operation to detect and correct significant clerical and analytical errors, and unusual laboratory results, in a timely manner?

NOTE: The laboratory must have a documented system in operation to detect and correct significant clerical and analytical errors, and unusual laboratory results. One common method is review of results by a qualified person (technologist, supervisor, pathologist) before release from the laboratory, but there is no requirement for supervisory review of all reported data. The selective use of delta checks also may be useful in detecting clerical errors in consecutive samples from the same patient/client. In computerized laboratories, there should be automatic "traps" for improbable results. The system for detecting clerical errors, significant analytical errors, and unusual laboratory results must provide for timely correction of errors, i.e., before results become available for clinical decision making. For suspected errors detected by the end user after reporting, corrections must be promptly made if such errors are confirmed by the laboratory.

Each procedure must include a listing of common situations that may cause analytically inaccurate results, together with a defined protocol for dealing with such analytic errors or interferences. This may require alternate testing methods; in some situations, it may not be possible to report results for some or all of the tests requested.

The intent of this requirement is NOT to require verification of all results outside the reference (normal) range.

COMMENTARY:

N/A


In the absence of on-site supervisors, are the results of tests performed by personnel reviewed by the laboratory director or general supervisor within 24 hours?

NOTE: The CAP does NOT require supervisory review of all test results before or after reporting to patient records. Rather, this question is intended to address only that situation defined under CLIA-88 for "high complexity testing" performed by trained high school graduates qualified under 42CFR493.1489(b)(5) when a qualified general supervisor is not present.

COMMENTARY:

In the absence of on-site supervisors, the results of tests performed by personnel must be reviewed by the laboratory director or general supervisor within 24 hours. The CAP does not require supervisory review of all test results before or after reporting to patient records. Rather, this question is intended to address only that situation defined under CLIA-88 for "high complexity testing" performed by trained



high school graduates qualified under 42CFR493.1489(b)(5) when a qualified general supervisor is not present.

REFERENCE: Department of Health and Human Services, Centers for Medicare and Medicaid Services. Clinical laboratory improvement amendments of 1988; final rule. Fed Register. 2003(Jan 24):7182 [42CFR493.1463(a)(3) and 42CFR493.1463(c)]: 7183 [42CFR493.1489(b)(1) and 42CFR493.1489(b)(5)].

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PROCEDURE MANUAL

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The procedure manual should be available to, and used by, personnel at the workbench and should include: principle, clinical significance, specimen type, required reagents, calibration, quality control, procedural steps, calculations, reference intervals, and interpretation. Pre-analytic, analytic, and post-analytic considerations should be provided. The specific style and format of procedure manuals are at the discretion of the laboratory director.

The inspection team should review the procedure manual in detail to understand the laboratory's standard operating procedures, ensure that all significant information and instructions are included, and that actual practice matches the contents of the procedure manuals.

**REVISED** 04/06/2006


Is a complete procedure manual available at the workbench or in the work area?

NOTE 1: The use of inserts provided by manufacturers is not acceptable in place of a procedure manual. However, such inserts may be used as part of a procedure description, if the insert accurately and precisely describes the procedure as performed in the laboratory. Any variation from this printed procedure must be detailed in the procedure manual. In all cases, appropriate reviews must occur.

NOTE 2: A manufacturer's procedure manual for an instrument/ reagent system may be acceptable as a component of the overall departmental procedures. Any modification to or deviation from the procedure manual must be clearly documented.

NOTE 3: Card files or similar systems that summarize key information are acceptable for use as quick reference at the workbench provided that:

a. A complete manual is available for referenceb. The card file or similar system corresponds to the complete manual and is subject to

document control



NOTE 4: Electronic (computerized) manuals are fully acceptable. There is no requirement for paper copies to be available for the routine operation of the laboratory, so long as the electronic versions are readily available to all personnel. However, procedures must be available to laboratory personnel when the electronic versions are inaccessible (e.g., during laboratory information system or network downtime); thus, the laboratory must maintain either paper copies or electronic copies on CD or other media that can be accessed via designated computers. Current paper copies of electronically stored procedures should be available at the time of the CAP inspection, or rapidly generated at the request of the inspector.

Electronic versions of procedures must be subjected to proper document control (i.e., only authorized persons may make changes, changes are dated/signed (manual or electronic), and there is documentation of annual review). Documentation of review of electronic procedures may be accomplished by including statements such as “reviewed by [name of reviewer] on [date of review]” in the electronic record. Alternatively, paper review sheets may be used to document review of electronic procedures. Documentation of review by a secure electronic signature is NOT required.

COMMENTARY:

N/A

REFERENCES: 1) Department of Health and Human Services, Centers for Medicare and Medicaid Services. Clinical laboratory improvement amendments of 1988; final rule. Fed Register. 2003(Jan 24):7164 [42CFR493.1251]; 2) van Leeuwen AM. 6 steps to building an efficiency tool. Advance/Laboratory. 1999:8(6):88-91; 3) Borkowski A, et al. Intranet-based quality management documentation at the Veterans Affairs Maryland health care system. Mod. Pathol. 2001;14:1-5; 4) NCCLS. Clinical laboratory technical procedure manuals - fourth edition; approved guideline GP2-A4. Wayne, PA: NCCLS, 2002.


Is there documentation of at least annual review of all policies and procedures in the immunology/syphilis serology laboratory section(s) by the current laboratory director or designee?

NOTE: The director must ensure that the collection of policies and technical protocols is complete, current, and has been substantially reviewed by a knowledgeable person. Technical approaches must be scientifically valid and clinically relevant. To minimize the burden on the laboratory and reviewer(s), it is suggested that a schedule be developed whereby roughly 1/12 of all procedures are reviewed monthly. Paper/electronic signature review must be at the level of each procedure, or as multiple signatures on a listing of named procedures. A single signature on a Title Page or Index of all procedures is not sufficient documentation that each procedure has been carefully reviewed. Signature or initials on each page of a procedure is not required.



COMMENTARY:

N/A

REFERENCES: 1) Department of Health and Human Services, Centers for Medicare and Medicaid Services. Clinical laboratory improvement amendments of 1988; final rule. Fed Register. 2003(Jan 24):7173 [42CFR493.1407(e)(13)]; 2) Borkowski A, et al. Intranet-based quality management documentation at the Veterans Affairs Maryland health care system. Mod. Pathol. 2001;14:1-5.


Does the director or designee review and approve all new policies and procedures, as well as substantial changes to existing documents, before implementation?

NOTE: Current practice must match the policy and procedure documents.

COMMENTARY:

N/A

REFERENCE: Department of Health and Human Services, Centers for Medicare and Medicaid Services. Clinical laboratory improvement amendments of 1988; final rule. Fed Register. 2003(Jan 24):7164 [42CFR493.1251(d)].


If there is a change in directorship, does the new director ensure (over a reasonable period of time) that laboratory procedures are well-documented and undergo at least annual review?

COMMENTARY:

N/A



When a procedure is discontinued, is a paper or electronic copy maintained for at least 2 years, recording initial date of use, and retirement date?



COMMENTARY:

N/A

REFERENCE: Department of Health and Human Services, Centers for Medicare and Medicaid Services. Clinical laboratory improvement amendments of 1988; final rule. Fed Register. 2003(Jan 24):7164 [42CFR493.1105(a)(2)].


Does the laboratory have a system documenting that all personnel are knowledgeable about the contents of procedure manuals (including changes) relevant to the scope of their testing activities?

NOTE: This does not specifically require annual procedure sign-off by testing personnel. The form of this system is at the discretion of the laboratory director.

COMMENTARY:

N/A

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SPECIMEN COLLECTION AND HANDLING

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Are procedures adequate to verify sample identity and integrity (includes capillary specimens, aliquots and dilutions)?

COMMENTARY:

Identification of specimens must be improved to ensure specimen identity and integrity (includes capillary specimens, aliquots, and dilutions).


Are there documented criteria for the rejection of unacceptable specimens and the special handling of sub-optimal specimens?



NOTE: This question does not imply that all "unsuitable" specimens are discarded or not analyzed. There must be a mechanism to notify clinical personnel responsible for patient care. If a test result is still desired by the ordering physician, then the condition of the sample must be stated on the report, and a notation made of any limitation in test result interpretation. The laboratory may wish to record that a dialogue was held with the physician, when such occurs.

COMMENTARY:

N/A

REFERENCES: 1) Department of Health and Human Services, Centers for Medicare and Medicaid Services. Clinical laboratory improvement amendments of 1988; final rule. Fed Register. 2003(Jan 24):7183 [42CFR493.1249(a) and (b)]; 2) Jones BA, et al. Chemistry specimen acceptability. A College of American Pathologists Q-Probes study of 453 laboratories. Arch Pathol Lab Med. 1997;121:19-26.


Is the disposition of all unacceptable specimens documented in the patient report and/or quality management records?

COMMENTARY:

N/A

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RESULTS REPORTING

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Are reference intervals (normal values) established or verified by the laboratory for the population being tested?

NOTE: Age- and sex-specific reference intervals (normal values) must be verified or established by the laboratory. If a formal reference interval study is not possible or practical, then the laboratory should carefully evaluate the use of published data for its own reference ranges, and document that review.

COMMENTARY:

N/A



REFERENCES: 1) Knight JA. Laboratory issues regarding geriatric patients. Lab Med. 1997;28:458-461; 2) NCCLS. How to define and determine reference intervals in the clinical laboratory; approved guideline C28-A2. Wayne, PA: NCCLS, 2000.


As appropriate, are all patient results reported with accompanying reference (normal) intervals or interpretations?

NOTE: The use of high and low flags (generally available with a computerized laboratory information system) is recommended.

COMMENTARY:

N/A

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REAGENTS

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The verification of reagent performance is required and must be documented. Any of several methods may be appropriate, such as direct analysis with reference materials, parallel testing of old vs. new reagents, and checking against routine controls. The intent of the questions is for new reagents to be checked by an appropriate method and the results recorded before patient results are reported. Where individually packaged reagents/kits are used, there should be criteria established for monitoring reagent quality and stability, based on volume of usage and storage requirements. Processing of periodic "wet controls" to validate reagent quality and operator technique is a typical component of such a system.


Are reagents and solutions properly labeled, as applicable and appropriate, with the following elements?

1. Content and quantity, concentration or titer2. Storage requirements3. Date prepared or reconstituted by laboratory4. Expiration date

NOTE: The above elements may be recorded in a log (paper or electronic), rather than on the containers themselves, providing that all containers are identified so as to be traceable to the appropriate data in the log. While perhaps useful for inventory management, labeling with "date received" is not routinely required. There is no requirement to routinely label individual containers



with "date opened"; however, a new expiration date must be recorded if opening the container changes the expiration date, storage requirement, etc. The inspector will describe specific issues of non-compliance in the Inspector's Summation Report.

COMMENTARY:

N/A


Are all reagents used within their indicated expiration date?

NOTE: The laboratory must assign an expiration date to any reagents that do not have a manufacturer-provided expiration date. The assigned expiration date should be based on known stability, frequency of use, storage conditions, and risk of contamination.

COMMENTARY:

N/A



Are reagents stored as recommended by the manufacturer?

NOTE: If ambient temperature is indicated, there must be documentation that the defined ambient temperature is maintained and corrective action is taken when tolerance limits are exceeded.

COMMENTARY:

N/A


Are new reagent lots and/or shipments checked against old reagent lots or with suitable reference material before or concurrently with being placed in service?

NOTE: New reagent lots and/or shipments must be tested in parallel with old lots before or concurrently with being placed in service to ensure that the calibration of the new lot of reagent has maintained consistent results for patient specimens. Good clinical laboratory science includes patient-



based comparisons when possible, since it is patient specimens that are tested. For quantitative tests, reagent validation is most reliably performed by assaying the same patient specimens with both the old and new lots to ensure consistent results. For qualitative tests, minimum cross-checking includes retesting at least one known positive and one known negative patient sample from the old reagent lot against the new reagent lot, ensuring that the same results are obtained with the new lot. A weakly positive sample should also be used in systems where patient results are reported in that fashion.

Some method manufacturers provide reference materials or QC products specifically intended to validate successful calibration of their methods; these should be used when available. Such materials have method-specific, and, where appropriate, reagent-lot-specific, target values. Thus, these materials should be used only with the intended methods.

Proficiency testing materials with peer group established mean values are acceptable for validation of new reagent lots.

Third party general-purpose reference materials may be suitable for validation of calibration following reagent lot changes if the material is documented in the package insert or by the method manufacturer to be commutable with patient specimens for the method. A commutable reference material is one that gives the same numeric result, as would a patient specimen containing the same quantity of analyte in the analytic method under discussion; e.g., matrix effects are absent. Commutability between a reference material and patient specimens can be demonstrated using the protocol in NCCLS EP14-A2.

QC material may be an acceptable alternative for validating calibration following reagent lot changes. However, the laboratory should be aware that QC material may be affected by matrix interference between different reagent lots. Thus, even if QC results show no change following a reagent lot change, a calibration inconsistency for patient specimens could exist nonetheless, masked by matrix interference affecting the QC material (a “false negative” validation). The use of patient samples to confirm the absence of matrix interference may be helpful.

COMMENTARY:

N/A

REFERENCE: Clinical and Laboratory Standards Institute (CLSI). Evaluation of Matrix Effects; Approved Guideline—Second Edition. CLSI document EP14-A2 (ISBN 1-56238-561-5). Clinical and Laboratory Standards Institute, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania, 19087-1898 USA, 2005.


Are the recommendations of the manufacturer for the proper use of reagents and controls in kit procedures followed?

COMMENTARY:



N/A

IMM.33270 Phase I N/A YES NO

Are common interferences evaluated for all analytes measured with each reagent system, or is credible information available from other sources?

NOTE: NCCLS Guideline EP7-A2 (Interference Testing In Clinical Chemistry) is a useful reference source. Neither this document nor its methods are mandatory for CAP accreditation.

COMMENTARY:

N/A

REFERENCE: Clinical and Laboratory Standards Institute (CLSI). Interference Testing in Clinical Chemistry; Approved Guideline—Second Edition. CLSI document EP7-A2 (ISBN 1-56238-584-4). Clinical and Laboratory Standards Institute, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087-1898 USA, , 2005.


If there are multiple components of a reagent kit, does the laboratory use only components of reagent kits within the kit lot unless otherwise specified by the manufacturer?

NOTE: It is not appropriate to mix components from different kit lot numbers except when approved by the manufacturer.

COMMENTARY:

N/A

REFERENCE: Department of Health and Human Services, Centers for Medicare and Medicaid Services. Clinical laboratory improvement amendments of 1988; final rule. Fed Register. 2003(Jan 24):7164 [42CFR493.1252(e)].

--------------------------------------------------------------

CALIBRATION AND STANDARDS

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NOTE: The following requirements for calibration, calibration verification and analytic measurement range validation apply only to analyses that provide truly quantitative measurements expressed in mass units per unit volume (e.g. gm/L or mg/ml) OR in units traceable to a reference preparation or



standard that is calibrated in mass units per unit volume. If these criteria are not met, the measurement is NOT quantitative and this section is not applicable.

This introduction discusses the processes of calibration, calibration verification, and analytical measurement range validation (AMR).

CALIBRATION is the set of operations that establish, under specified conditions, the relationship between reagent system/instrument response and the corresponding concentration/activity values of an analyte. Calibration procedures are typically specified by a method manufacturer, but may also be established by the laboratory.

The term “calibration” has the same meaning in this checklist as in the U.S. CLIA-88 regulations.

However, the term “calibration verification,” as used in this checklist, carries a more restrictive meaning than in CLIA-88. As defined in the January, 2003 revision of CLIA-88, “calibration verification” refers to 2 distinct processes: 1) verification of correct method calibration and 2) validation of the reportable range. This checklist restricts the use of the term “calibration verification” to the first process. The checklist uses a different term, “analytical measurement range (AMR) validation,” to refer to the second process.

All of these processes—calibration, calibration verification, and AMR validation--are required to ensure the continued accuracy of a test method. These concepts are further elaborated below.

In this checklist, CALIBRATION VERIFICATION denotes the process of confirming that the current calibration settings remain valid for a method. If calibration verification confirms that the current calibration settings are valid, it is not necessary to perform a complete calibration or recalibration of the method. Calibration verification can be accomplished in several ways. If the method manufacturer provides a calibration validation or verification process, it should be followed. Other techniques include (1) assay of the current method calibration materials as unknown specimens, and determination that the correct target values are recovered, and (2) assay of matrix-appropriate materials with target values that are specific for the method.

Each laboratory must define limits for accepting or rejecting tests of calibration verification.

Materials for calibration verification must have a matrix appropriate for the clinical specimens assayed by that method, and target values appropriate for the measurement system. Materials may include, but are not limited to:

1. Calibrators used to calibrate the analytical measurement system2. Materials provided by the analytical measurement system vendor for the purpose of

calibration verification3. Previously tested unaltered patient/client specimens4. Primary or secondary standards or reference materials with matrix characteristics and

target values appropriate for the method,5. Proficiency testing material or proficiency testing validated material with matrix

characteristics and target values appropriate for the method



In general, routine control materials are not suitable for calibration verification, except in situations where the material is specifically designated by the method manufacturer as suitable for verification of the method's calibration process.

The ANALYTICAL MEASUREMENT RANGE (AMR) is the range of analyte values that a method can directly measure on the specimen without any dilution, concentration, or other pretreatment not part of the usual assay process. AMR VALIDATION is the process of confirming that the assay system will correctly recover the concentration or activity of the analyte over the AMR. The materials used for validation must be known to have matrix characteristics appropriate for the method. The matrix of the sample (i.e., the environment in which the sample is suspended or dissolved) may influence the measurement of the analyte. In many cases, the method manufacturer will recommend suitable materials. The test specimens must have analyte values which, at a minimum, are near the low, midpoint, and high values of the AMR. Specimen target values can be established by comparison with peer group values for reference materials, by assignment of reference or comparative method values, and by dilution or admixture ratios of one or more specimens with known values. Each laboratory must define limits for accepting or rejecting validation tests of the AMR.

Materials for AMR validation should have a matrix appropriate for the clinical specimens assayed by that method, and target values appropriate for the measurement system. Materials may include, but are not limited to:

1. Linearity material of appropriate matrix, e.g., CAP Survey-based or other suitable linearity verification material

2. Proficiency testing survey material or proficiency testing survey-validated material3. Previously tested patient/client specimens, unaltered4. Previously tested patient/client specimens, altered by admixture with other specimens,

dilution, spiking in known amounts of an analyte, or other technique5. Primary or secondary standards or reference materials with matrix characteristics and

target values appropriate for the method6. Calibrators used to calibrate the analytic measurement system7. Control materials, if they adequately span the AMR.

RECALIBRATION / CALIBRATION VERIFICATION and AMR VALIDATION INTERVALS: Recalibration or calibration verification, and AMR validation, must be performed at least once every 6 months, as specified under CLIA-88 regulations at 42CFR493.1255(b)(3). Successful calibration verification certifies that the calibration is still valid; unsuccessful calibration verification requires remedial action, which usually includes recalibration and AMR revalidation. The performance of recalibration or a calibration verification procedure resets the calendar to a new maximum 6-month interval before the next required reassessment. Methods that are recalibrated more frequently than every 6 months do not require a separate calibration verification procedure.

In addition to the every 6 month requirement, laboratories must perform recalibration or calibration verification and AMR validation at changes in major system components, and at changes of lots of chemically or physically active reagents unless the laboratory can demonstrate that changing reagent lot numbers does not affect the range used to report patient/client test results. The laboratory director



should determine what constitutes a major system component change or a change in reagents that would require calibration verification and revalidation of the AMR. Manufacturers’ instructions should be followed.

The laboratory should establish other criteria, as appropriate, for recalibration/calibration verification. These include but are not limited to failure of quality control to meet established criteria, and major maintenance or service to the instrument.

**NEW** 04/06/2006


Are calibration procedures for each method adequate, and are the calibration results documented?

COMMENTARY:

N/A

REFERENCES: 1) Department of Health and Human Services, Centers for Medicare & Medicaid Services. Clinical laboratory improvement amendments of 1988; final rule. Fed Register. 1992(Feb 28):7165 [42CFR493.1217]; 2) Department of Health and Human Services, Centers for Medicare & Medicaid Services. Medicare, Medicaid and CLIA Programs; Laboratory Requirements Relating to Quality Systems and Certain Personnel Qualifications; final rule. Fed Register. 2003(Jan 24):3707 [42CFR493.1255]; 3) Kroll MH, Emancipator K. A theoretical evaluation of linearity. Clin Chem. 1993;39:405-413; 4) Clinical and Laboratory Standards Institute (CLSI). Evaluation of Matrix Effects; Approved Guideline—Second Edition. CLSI document EP14-A2 (ISBN 1-56238-561-5). Clinical and Laboratory Standards Institute, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania, 19087-1898 USA, 2005; 5) Miller WG. “Quality control.” Professional Practice in Clinical Chemistry: A Companion Text, ed DR Dufour. Washington, DC: AACC Press, 1999:12-1 to 12-22; 6) Kroll MH, et al. Evaluation of the extent of nonlinearity in reportable range studies. Arch Pathol Lab Med. 2000;124:1331-1338.

**NEW** 04/06/2006


Are high quality materials with method- and matrix-appropriate target values used for calibration and calibration verification whenever possible?

NOTE: Calibration materials establish the relationship between method/instrument response and the corresponding concentration/activities of an analyte. They have defined analyte target values and appropriate matrix characteristics for the clinical specimens and specific assay method. Many



instrument systems require calibration materials with system-specific target values to produce accurate results for clinical specimens.

COMMENTARY:

N/A

REFERENCE: Clinical and Laboratory Standards Institute (CLSI). Evaluation of Matrix Effects; Approved Guideline—Second Edition. CLSI document EP14-A2 (ISBN 1-56238-561-5). Clinical and Laboratory Standards Institute, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania, 19087-1898 USA, 2005.

**NEW** 04/06/2006


Are all calibration materials properly labeled as to content and calibration values?

NOTE: Complete values need not necessarily be recorded directly on each vial of calibrator material, so long as there is a clear indication where specific values may be found for each analyte tested and each analyzer used by the laboratory.

COMMENTARY:

N/A

**NEW** 04/06/2006


Do calibration materials include dates placed in service and expiration dates?

NOTE: The dates may be recorded in a log (paper or electronic), rather than on the containers themselves, providing that all containers are identified so as to be traceable to the appropriate data in the log.

COMMENTARY:

N/A



**NEW** 04/06/2006


Are criteria established for frequency of recalibration or calibration verification, and the acceptability of results?

NOTE: Criteria typically include:

1. At changes of reagent lots for chemically or physically active or critical components, unless the laboratory can demonstrate that the use of different lots does not affect the accuracy of patient/client test results and the range used to report patient/client test data

2. QC fails to meet established criteria3. After major maintenance or service4. When recommended by the manufacturer5. At least every 6 months

Materials that may be used for calibration verification include, but are not limited to:

1. Calibrators used to calibrate the analytical measurement system2. Materials provided by the analytical measurement system vendor for the purpose of

calibration verification3. Previously tested unaltered patient/client specimens4. Primary or secondary standards or reference materials with matrix characteristics and

target values appropriate for the method, proficiency testing material or proficiency testing validated material with matrix characteristics and target values appropriate for the method

In general, routine control materials are not suitable for calibration verification, except in situations where the material is specifically designated by the method manufacturer as suitable for verification of the method's calibration process.

COMMENTARY:

N/A

REFERENCES: 1) Department of Health and Human Services, Centers for Medicare and Medicaid Services. Clinical laboratory improvement amendments of 1988; final rule. Fed Register. 2003(Jan 24):3707[42CFR493.1255(b)(3)]; 2) Miller WG. “Quality control.” Professional Practice in Clinical Chemistry: A Companion Text, ed DR Dufour. Washington, DC: AACC Press, 1999:12-1 to 12-22.



**NEW** 04/06/2006


Is the method system recalibrated when calibration verification fails to meet the established criteria of the laboratory?

COMMENTARY:

N/A

**REVISED** 04/06/2006


Is validation of the analytical measurement range (AMR) performed with matrix-appropriate materials which include the low, mid and high range of the AMR, and is the process documented?

NOTE: The AMR is the range of analyte values that a method can directly measure on the specimen without any dilution, concentration, or other pretreatment that is not part of the usual assay process. Validation of the AMR is the process of confirming that the assay system will correctly recover the concentration or activity of the analyte over the AMR.

The materials used for validation must be known to have matrix characteristics appropriate for the method. The test specimens must have analyte values that as a minimum are near the low, midpoint, and high values of the AMR. Guidelines for analyte levels near the low and high range of the AMR should be determined by the laboratory director. Factors to consider are the expected analytic imprecision near the limits, the clinical impact of errors near the limits, and the availability of test specimens near the limits. It may be difficult to obtain specimens with values near the limits for some analytes (e.g., T uptake, free thyroxine, prolactin, FSH). In such cases, reasonable procedures should be adopted based on available specimen materials. The method manufacturer’s instructions for validating the AMR should be followed, when available. Specimen target values can be established by comparison with peer group values for reference materials, by assignment of reference or comparison method values, and by dilution ratios of one or more specimens with known values. Each laboratory must define limits for accepting or rejecting validation tests of the AMR.

The AMR must be revalidated at least every 6 months, and following changes in major system components or lots of analytically critical reagents (unless the laboratory can demonstrate that changing reagent lot numbers does not affect the range used to report patient test results, and control values are not adversely affected).

If the materials used for calibration or for calibration verification include low, midpoint, and high values that are near the stated AMR, then separate AMR validation is not required.



Materials that may be used for AMR validation include, but are not limited to:

1. Linearity material of appropriate matrix, e.g., CAP Survey-based or other suitable linearity verification material

2. Proficiency testing survey material or proficiency testing survey-validated material3. Previously tested patient/client specimens, unaltered4. Previously tested patient/client specimens, altered by admixture with other specimens,

dilution, spiking in known amounts of an analyte, or other technique5. Primary or secondary standards or reference materials with matrix characteristics and

target values appropriate for the method6. Calibrators used to calibrate the analytic measurement system7. Control materials, if they adequately span the AMR

COMMENTARY:

N/A

REFERENCE: Department of Health and Human Services, Centers for Medicare and Medicaid Services. Clinical laboratory improvement amendments of 1988; final rule. Fed Register. 2003(Jan 24):3707 [42CFR493.1255].

**NEW** 04/06/2006


Are criteria established for validating the analytical measurement range, and is compliance documented?

NOTE: Some instruments have integral automatic dilution systems when a result exceeds the AMR. Validation of the AMR refers to the inherent measurement range of the method, not to the range extended by an automatic dilution process. A separate validation of the automatic dilution process should be performed.

COMMENTARY:

N/A

**NEW** 04/06/2006


Are results falling outside the AMR limits reviewed and reassayed if necessary before reporting?



NOTE: Apparent analyte values that are lower or higher than the AMR do not routinely require repeat analysis if the result is reported as less than the lower limit, or greater than the upper limit, respectively, and the laboratory has evidence that the low result is not due to sampling/dilution errors, immunologic "hook effects," etc. In special cases, the procedure should state if an analyte cannot be diluted or concentrated, or if there are limitations to the amount of dilution or concentration that can be successfully used.

The CLINICALLY REPORTABLE RANGE (CRR) is the range of analyte values that a method can report as a quantitative result, allowing for specimen dilution, concentration or other pretreatment used to extend the direct AMR. For example, if it is desired to report a result that exceeds the AMR, the specimen is commonly diluted to bring the analyte into that range, the diluted specimen is reassayed, and the final result calculated using the dilution factor.

The establishment of the CRR is a medical judgment made by the Laboratory Director, and is based in part on the assay technology. The CRR is typically established at the time of initial method validation, and it does not need to be re-evaluated unless the methodology changes for the analyte. The method manufacturer frequently will specify the AMR and procedures to use for dilution or concentration of specimens with values outside the AMR.

The lower limit of the CRR is typically the lower limit of the AMR of the method, as verified during method validation and stated in the procedure manual. Values lower than this limit will be reported as less than the limit. The upper limit of the CRR is typically not specified unless there is a measurement limitation of a dilution protocol for an analyte. It is acceptable to dilute until a value in the AMR is achieved. The diluent should be specified for each analyte that can be successfully diluted to bring its quantity into the AMR.

An example of a CRR with both low and high limits is given for hCG as follows: Assume that the AMR is 3-1,000 mIU/mL. A Laboratory Director establishes that, for proper patient/client care, the CRR is 5-1,000,000 mIU/mL. The lower CRR is based on medical judgment that lower values are not diagnostic for pregnancy, while values above the upper CRR are not useful for diagnostic or prognostic purposes. Patient/client specimens with analytical measured results of <3, 3, or 4 mIU/mL are reported as "<5 mIU/mL"; specimens with analytic results >1,000 are diluted and rerun to obtain quantitative values up to 1,000,000 mIU/mL; specimens with analytic results >1,000,000 mIU/mL are reported as ">1,000,000 mIU/mL".

COMMENTARY:

N/A

REFERENCE: Department of Health and Human Services, Centers for Medicare and Medicaid Services. Clinical laboratory improvement amendments of 1988; final rule. Fed Register. 2003(Jan 24):7164 [42CFR493.1253(a)].




Are dilution protocols and diluents (or concentration protocols) specified for all methods for which the CRR exceeds the AMR?

NOTE: When a test result exceeds the AMR, the laboratory may dilute or concentrate the specimen to adjust the analyte content to be within the AMR, then repeat the assay to obtain a quantitative result. The procedure manual must include the protocol for dilution or concentration, any diluents or other components used in the process, and the calculation of the final reportable result. If there is a limit to the amount of dilution or concentration that is appropriate for a method, the procedure must state the limit, and specify how to report results that exceed the CRR.

COMMENTARY:

N/A

--------------------------------------------------------------

CONTROLS

--------------------------------------------------------------

Controls are samples that act as surrogates for patient specimens. They are periodically processed like a patient sample to monitor the ongoing performance of the entire analytic process.

Most quantitative tests are traditionally monitored with 2 levels of liquid control material (procedural control). This is done at a frequency within which the accuracy and precision of the measuring system is expected to be stable (based upon manufacturer's recommendations), but at least each day that patient testing is performed. The daily use of two levels of liquid control may NOT be required for certain test systems, where the daily use of instrument, and/or electronic controls is documented as sufficient to demonstrate that calibration status is maintained within acceptable limits.

The daily use of 2 levels of instrument and/or electronic controls as the only QC system is acceptable only for unmodified test systems cleared/approved by the FDA and classified under CLIA-88 as "waived" or "moderate complexity". The laboratory is expected to provide documentation of its validation of all instrument-reagent systems for which daily controls are limited to instrument and/or electronic controls, and the Inspector will review these data to assess the adequacy of the QC system. This documentation must include the Federal complexity classification of the testing system AND data showing that calibration status is monitored.


For QUANTITATIVE tests, are control materials at more than one concentration (level) used for all tests at least daily?



NOTE: Controls should verify assay performance at relevant decision points. This may be determined based on clinical or administrative criteria. Control testing is not necessary on days when patient testing is not performed.

The daily use of 2 levels of instrument and/or electronic controls as the only QC system is acceptable only for unmodified test systems cleared by the FDA and classified under CLIA-88 as "waived" or "moderate complexity". The laboratory is expected to provide documentation of its validation of all instrument-reagent systems for which daily controls are limited to instrument and/or electronic controls. For laboratories subject to CLIA-88, this documentation must include the Federal complexity classification of the testing system and data showing that calibration status is monitored. Controls should verify assay performance at relevant decision points. This may be determined based on clinical criteria or administrative criteria.

COMMENTARY:

N/A

REFERENCES: 1) Department of Health and Human Services, Centers for Medicare and Medicaid Services. Medicare, Medicaid and CLIA programs; CLIA fee collection; correction and final rule. Fed Register. 1993(Jan 19):5232 [42CFR493.1256(d)(3)(i)]; 2) NCCLS. Statistical Quality Control for Quantitative Measurements: Principles and Definitions; Approved Guideline--Second Edition. NCCLS document C24-A2 [ISBN 1-56238-371-X]. NCCLS, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania, 19087, USA, 1999.

**REVISED** 04/06/2006


For quantitative tests, has a valid acceptable range been established or verified for each lot of control material?

NOTE: For unassayed controls, the laboratory must establish a valid acceptable range by repetitive analysis in runs that include previously tested control material. This may be established through various mechanisms, such as multiple individual replicates or use of moving averages. For assayed controls, the laboratory must verify the recovery ranges supplied by the manufacturer.

COMMENTARY:

N/A

REFERENCES: 1) NCCLS. Evaluation of Precision Performance of Clinical Chemistry Devices; Approved Guideline—Second Edition. NCCLS document EP5-A2 (ISBN 1-56238-542-9). NCCLS, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087-1898 USA, 2004; 2) NCCLS. User demonstration of performance for precision and accuracy; approved guideline EP15-A. Wayne, PA: NCCLS, 2002; 3) Ross JW, Lawson NS. Analytic goals, concentration relationships, and the state of



the art of clinical laboratory precision. Arch Pathol Lab Med 1995;119:495-513; 4) Steindel SJ, Tetrault G. Quality control practices for calcium, cholesterol, digoxin, and hemoglobin. A College of American Pathologists Q-Probes study in 505 hospital laboratories. Arch Pathol Lab Med 1998;122:401-408; 5) NCCLS. Quality Management for Unit-Use Testing; Approved Guideline. NCCLS document EP18-A (ISBN 1-56238-481-3). NCCLS, 940 West Valley Road, Suite 1400, Wayne, PA 19087-1898 USA, 2002.


Are controls properly labeled as to content, lot number, date of preparation and expiration date?

COMMENTARY:

N/A


Are reactive, weakly reactive and nonreactive controls all used in test systems where results are reported in that fashion?

NOTE: Weakly reactive controls should be used when test results are reported in that fashion, unless such controls are not commercially available.

COMMENTARY:

N/A


Are there records to reflect the results of all control procedures?

COMMENTARY:

Results of controls must be recorded for all assays.

**REVISED** 04/06/2006


Is there documented evidence of corrective action taken when results of controls exceed defined tolerance limits?



NOTE: When a QC result is unacceptable, patient/client test results obtained since the last acceptable test run must be re-evaluated to determine if there is a significant clinical difference in patient/client results.

COMMENTARY:

N/A

REFERENCE: Department of Health and Human Services, Centers for Medicare and Medicaid Services. Clinical laboratory improvement amendments of 1988; final rule. Fed Register. 2003(Oct 1):1046 [42CFR493.1282(b)(2)].


Are control specimens tested in the same manner and by the same personnel as patient samples?

NOTE: It is implicit in quality control that control specimens are tested in the same manner as patient specimens. Moreover, QC specimens must be analyzed by personnel who routinely perform patient testing. This does not imply that each operator must perform QC daily, so long as each instrument and/or test system has QC performed at required frequencies. To the extent possible, all steps of the testing process must be controlled, recognizing that pre-analytic and post-analytic variables may differ from those encountered with patient samples.

COMMENTARY:

N/A

REFERENCE: Department of Health and Human Services, Centers for Medicare and Medicaid Services. Clinical laboratory improvement amendments of 1988; final rule. Fed Register. 2003(Jan 24):7166 [42CFR493.1256(d)(8)].


Are the results of controls verified for acceptability before reporting results?

NOTE: It is implicit in quality control that patient test results will not be reported when controls yield unacceptable results.

COMMENTARY:

N/A



REFERENCE: Department of Health and Human Services, Centers for Medicare and Medicaid Services. Clinical laboratory improvement amendments of 1988; final rule. Fed Register. 2003(Jan 24):7166 [42CFR493.1256(f)].


For tests that do NOT include positive and negative controls built into the test device, are known positive and negative controls tested on each day of analysis for all qualitative or semi-quantitative antigen/antibody tests (e.g., rheumatoid factor, ASO, hCG, heterophile antibody)?

NOTE: Using the Summation Report, the Inspector will identify which specific serologic tests fail to meet this requirement.

COMMENTARY:

N/A

REFERENCE: Department of Health and Human Services, Centers for Medicare and Medicaid Services. Medicare, Medicaid and CLIA programs; CLIA fee collection; correction and final rule. Fed Register. 1993(Jan 19):5232 [42CFR493.1256(d)(3)(ii)].


For tests that DO include positive and negative controls built into the test device, is a positive and negative external control tested with each new kit lot number or different shipment of a given lot number for all qualitative or semi-quantitative antigen-antibody tests (e.g., rheumatoid factor, rapid plasma reagin, ASO, hCG, heterophile antibody, etc.)?

NOTE: Manufacturers' instructions must be followed. For panels or batteries, controls must be employed for each antigen or antibody sought in patient specimens. Such systems must have been classified as unmodified moderate complexity or waived tests for laboratories subject to CLIA-88.

COMMENTARY:

N/A

**NEW** 04/06/2006


Are quality control data reviewed and assessed at least monthly by the laboratory director or designee?



COMMENTARY:

N/A


Are all histochemical stains checked for intended reactivity each day of use?

COMMENTARY:

N/A

REFERENCE: Department of Health and Human Services, Centers for Medicare and Medicaid Services. Clinical laboratory improvement amendments of 1988; final rule. Fed Register. 2003(Jan 24):7166 [42CFR493.1256(e)(2)].

**REVISED** 04/06/2006


Are positive and negative controls included with each patient run for all fluorescent or enzyme antibody stains? NOTE: Internal antigens, when present, may serve as positive controls (e.g., IgA in tubular casts, IgG in protein droplets, and C3 in blood vessels). Non-reactive elements in the patient specimen may serve as a negative tissue control. A negative reagent control in which the patient tissue is processed in an identical manner to the test specimen but with the primary antibody omitted must be performed for each patient test specimen.

COMMENTARY:

N/A

REFERENCES: 1) NCCLS. Assessing the Quality of Immunoassay Systems: Radioimmunoassays and Enzyme, Fluorescence, and Luminescence Immunoassays; Approved Guideline. NCCLS document I/LA23A (ISBN 1-56238-533-X). NCCLS, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087-1898 USA, 2004; 2) Walker PD, et al. Practice guidelines for the renal biopsy. Mod. Pathol. 2004;17:1555-1563.




If the laboratory performs test procedures for which calibration or control materials are not commercially available, have guidelines been established to verify the accuracy of patient test results?

COMMENTARY:

N/A


If the laboratory uses more than one method to test for a given analyte, are the methods checked against each other at least twice a year for correlation of patient/client results?

NOTE: This question applies to quantitative tests performed on the same or different instrument makes/models. The use of fresh human samples (whole blood, serum, plasma, urine, etc.), rather than stabilized commercial controls, is important to directly address the issue of whether a patient/client sample yields the same results on all of the laboratory's instruments. Statistical agreement of commercial control materials across instruments does not guarantee comparability of patient/client specimen results because of potential matrix effects. In cases when pre-analytical stability of patient/client specimens is a limiting factor, alternative protocols based on QC or reference materials may be necessary but the materials used should be validated to have the same response as fresh human samples for the instruments/methods involved.

COMMENTARY:

N/A

REFERENCE: Department of Health and Human Services, Centers for Medicare and Medicaid Services. Medicare, Medicaid and CLIA programs; CLIA fee collection; correction and final rule. Fed Register. 1993(Jan 19):5236 [42CFR493.1281(a)].

--------------------------------------------------------------

INSTRUMENTS AND EQUIPMENT

--------------------------------------------------------------

A variety of instruments and equipment are used to support the performance of analytical procedures. All instruments and equipment should be properly operated, maintained, serviced, and monitored to ensure that malfunctions of these instruments and equipment do not adversely affect the analytical results. The inspection team should review the procedures for instrument/equipment operations, maintenance, and monitoring records to ensure that these devices are properly used. The procedures and schedules for instrument maintenance must be as thorough and as frequent as specified by the manufacturer.




Is an appropriate thermometric standard device of known accuracy (NIST-certified or guaranteed by manufacturer to meet NIST Standards) available?

NOTE: Thermometers should be present on all temperature-controlled instruments and environments and checked daily. Thermometric standard devices should be recalibrated or recertified prior to the date of expiration of the guarantee of calibration.

COMMENTARY:

N/A


Are all non-certified thermometers in use in the laboratory checked against an appropriate thermometric standard device before being placed in service?

COMMENTARY:

N/A


Is the temperature of water baths and/or heat blocks, refrigerators and other temperature-dependent equipment checked and recorded appropriately?

NOTE: Temperature-dependent equipment containing reagents and patient specimens must be monitored daily, as equipment failures could affect accuracy of patient test results. Items such as water baths and heat blocks used for procedures need only be checked on days of patient testing.

COMMENTARY:

N/A



**NEW** 04/06/2006


Are mechanical timers on serologic centrifuges, and the speed of the centrifuge, checked for accuracy every 6 months?

NOTE: Most serologic centrifuges and timers do not require frequent recalibration. Accuracy of speed and timing must be checked initially, after adjustments/repairs or implementation of new techniques, and periodically thereafter. The frequency of periodic checks should be based on the historical stability of the centrifuge, but at least every 6 months.

COMMENTARY:

N/A

REFERENCE: Food and Drug Administration. Current good manufacturing practice for blood and blood components. Equipment. Washington, DC: US Government Printing Office, 2000(Apr 1):[21CFR606.60(b)].


Are function checks performed at specified periodic intervals on all instruments?

COMMENTARY:

N/A


Are all instruments on a routine maintenance program?

COMMENTARY:

N/A


Are instrument maintenance, service and repair records (or copies) promptly available to, and usable by, the technical staff operating the equipment?



NOTE: Effective utilization of instruments by the technical staff depends upon the prompt availability of maintenance, repair, and service documentation (copies are acceptable). Laboratory personnel are responsible for the reliability and proper function of their instruments and must have access to this information. Off-site storage, such as with centralized medical maintenance or computer files, is not precluded if the inspector is satisfied that the records can be promptly retrieved.

COMMENTARY:

N/A


Are glass volumetric pipettes of certified accuracy (Class A); or are they checked by gravimetric, colorimetric, or some other verification procedure before initial use?

NOTE: The following Table shows the American Society for Testing and Materials' calibration (accuracy) specifications for Class A volumetric pipettes:

Nominal Capacity (mL) Variation (± mL)

0.5 - 2 0.006

3 - 7 0.01

8 – 10 0.02

15 - 30 0.03

40 - 50 0.05

100 0.08 Reconstitution of lyophilized calibrators, controls, or proficiency testing materials, or any other tasks requiring accurate volumetric measurement, must be performed only with measuring devices of Class A accuracy, or those for which accuracy has been defined and deemed acceptable for the intended use.

COMMENTARY:

N/A

REFERENCES: 1) Curtis RH. Performance verification of manual action pipettes. Part I. Am Clin Lab. 1994;12(7):8-9; 2) Curtis RH. Performance verification of manual action pipettes. Part II. Am Clin Lab. 1994;12(9):16-17; 3) Perrier S, et al. Micro-pipette calibration using a ratiometric photometer-reagent system as compared to the gravimetric method. Clin Chem. 1995;41:S183; 4) American Society for Testing and Materials. Standard specification for glass volumetric (transfer) pipettes, designation E 969-95. Philadelphia, PA: ASTM, 1995; 5) Johnson B. Calibration to dye for: Artel's new pipette calibration system. Scientist. 1999;13(12):14; 6) Connors M, Curtis R. Pipetting error: a



real problem with a simple solution. Parts I and II. Am Lab News. 1999;31(13):20-22; 7) Skeen GA, Ashwood ER. Using spectrophotometry to evaluate volumetric devices. Lab Med. 2000;31:478-479.


Are non-class A pipettes that are used for quantitative dispensing of material checked for accuracy and reproducibility at specified intervals, and results documented?

NOTE: Such checks are most simply done gravimetrically. This consists of transferring a number of measured samples of water from the pipette to a balance. Each weight is recorded, the weights are converted to volumes, and then means (for accuracy), and SD/CV (for imprecision) are calculated. Alternative approaches include spectrophotometry or (less frequently) the use of radioactive isotopes, and commercial kits are available from a number of vendors. Computer software is useful where there are many pipettes, and provides convenient documentation.

This checklist question does not apply to applications not requiring the accuracy of class A pipettes (e.g., serologic pipettes). Refer to the next checklist question.

COMMENTARY:

N/A

REFERENCES: 1) Curtis RH. Performance verification of manual action pipets. Part I. Am Clin Lab. 1994;12(7):8-9; 2) Curtis RH. Performance verification of manual action pipets. Part II. Am Clin Lab. 1994;12(9):16-17; 3) Perrier S, et al. Micro-pipette calibration using a ratiometric photometer-reagent system as compared to the gravimetric method. Clin Chem. 1995;41:S183; 4) Bray W. Software for the gravimetric calibration testing of pipets. Am Clin Lab. Oct 1995 (available on the internet at http://www.labtronics.com/pt_art.htm); 5) Kroll MH, et al (eds). Laboratory instrument evaluation, verification & maintenance manual, 5th edition. Northfield, IL: College of American Pathologists, 1999:126-127; 6) Johnson B. Calibration to dye for: Artel's new pipette calibration system. Scientist. 1999;13(12):14; 7) Connors M, Curtis R. Pipetting error: a real problem with a simple solution. Parts I and II. Am Lab News. 1999;31(13):20-22; 8) Skeen GA, Ashwood ER. Using spectrophotometry to evaluate volumetric devices. Lab Med. 2000;31:478-479.

**NEW** 04/06/2006


Is the use of less precise measuring devices such as serological plastic pipettes and graduated cylinders limited to situations where the accuracy and precision of calibrated glass pipettes are not required?


http://www.labtronics.com/pt_art.htm


NOTE: In contrast with the more stringent accuracy requirements of glass pipettes, ASTM requirements for plastic pipettes are ± 3% of the stated volume. The procedure manual should specify when the use of non-class A measuring devices is permissible.

COMMENTARY:

N/A

REFERENCE: American Society for Testing and Materials. Standard specification for serological pipets, disposable plastic, designation E 934-88, In 1993 Annual Book of ASTM Standards, section 14 (general methods and instrumentation). Philadelphia, PA: ASTM, 1993:14.02:485-486.


Are automatic and adjustable pipetting devices checked at specified periodic intervals for accuracy and reproducibility, and results recorded?

COMMENTARY:

Automatic and adjustable pipetting devices must be checked at specified periodic intervals for accuracy and reproducibility and the results of such testing documented.

REFERENCES: 1) Curtis RH. Performance verification of manual action pipets. Part I. Am Clin Lab. 1994;12(7):8-9; 2) Curtis RH. Performance verification of manual action pipets. Part II. Am Clin Lab. 1994;12(9):16-17; 3) Perrier S, et al. Micro-pipette calibration using a ratiometric photometer-reagent system as compared to the gravimetric method. Clin Chem. 1995;41:S183; 4) Bray W. Software for the gravimetric calibration testing of pipets. Am Clin Lab. Oct 1995 (available on the internet at http://www.labtronics.com/pt_art.htm); 5) Kroll MH, et al (eds). Laboratory instrument evaluation, verification & maintenance manual, 5th edition. Northfield, IL: College of American Pathologists, 1999:126-127; 6) Johnson B. Calibration to dye for: Artel's new pipette calibration system. Scientist. 1999;13(12):14; 7) Connors M, Curtis R. Pipetting error: a real problem with a simple solution. Parts I and II. Am Lab News. 1999;31(13):20-22; 8) Skeen GA, Ashwood ER. Using spectrophotometry to evaluate volumetric devices. Lab Med. 2000;31:478-479.


Has the laboratory evaluated its automatic pipetting systems for carryover?

NOTE: The laboratory should have procedures in place for evaluating whether carryover effects are present. This question applies to both stand-alone pipette systems and to sample pipettes integrated with analytic instruments.


http://www.labtronics.com/pt_art.htm


In practice, carryover is a problem only for analytes with a very wide clinical range of analyte concentration, such that a minute degree of carry-over could have significant clinical implications (for example, serologic tumor markers). The laboratory should select representative examples of such analytes for carryover studies.

Evaluation for carryover is not required for automatic pipettes that use disposable tips.

One suggested method to study carryover is to run known high patient samples, followed by known low samples to see if the results of the low-level material are affected. If carryover is detected, the laboratory should determine the analyte concentration above which subsequent samples may be affected, and define this value in the procedure. Results of each analytical run should be reviewed to ensure that no results exceed this level. If results that exceed the defined level are detected, then the appropriate course of action should be defined (repeat analysis of subsequent samples, for example).

Carryover studies should be performed, as applicable, as part of the initial evaluation of an instrument. (The laboratory may use the data from carryover studies performed by instrument manufacturers, as appropriate.) It is recommended that carryover studies be repeated periodically thereafter, particularly after major maintenance or repair.

COMMENTARY:

N/A


Are glass volumetric flasks of certified accuracy (Class A, National Institute of Standards and Technology (NIST) standard or equivalent), or if non-certified volumetric glassware is used, are all items checked for accuracy of calibration before initial use?

COMMENTARY:

N/A

.................................................................

Analytic Balances

.................................................................


Are balances cleaned, serviced and checked periodically only by qualified service personnel (i.e., service contract or as needed)?

COMMENTARY:



Balances should be cleaned, serviced, and recalibrated only by experienced personnel.


Are analytic balances mounted such that vibrations do not interfere with readings?

COMMENTARY:

Analytic balances should be mounted so that vibrations do not interfere with readings.

**REVISED** 04/06/2006


Are standard weights of the appropriate ANSI/ASTM Class available and used for checking accuracy?

NOTE: The verification of accuracy of the analytical balance must be performed on a regular schedule to ensure accurate creation of analytical calibrators and/or weighed-in controls from standard materials, as well as when gravimetrically checking the accuracy of pipettes.

There are three general types of balances in use. First, many contemporary balance designs use force transducers of various designs to provide mass readings. These balances typically have built-in certified calibration weights that are utilized automatically each time of use. The second type of balance employs a force transducer design that uses external weights for calibration each time the balance is used. Typically a single mass at the maximum weighing range, in conjunction with a zero point for the pan, is used for calibration of a force transducer balance design. The third type of balance, an older design, is a mechanical balance beam with internal moveable or external calibration weights. This design may have an electronic read-out.

In all cases, verification of accuracy over the weighing range with external calibrated masses is required on a periodic schedule appropriate to the use of the balance. Balances must be checked at least every 6 months, if used for weighing out materials to make up standard solutions for method calibration. For other purposes, annual verification may be adequate. Accuracy must be verified when a new balance is installed and whenever a balance is moved.

External validation of accuracy requires the appropriate class of ASTM specification weights. ASTM Class 1 weights are appropriate for calibrating high precision analytical balances (0.01 to 0.1 mg limit of precision). ASTM Class 2 weights are appropriate for calibrating precision top-loading balances (0.001 to 0.01 g precision). ASTM Class 3 weights are appropriate for calibrating moderate precision balances, (0.01 to 0.1 g precision).



Periodic external validation of accuracy is required to ensure that internal weights have not deteriorated from adsorption of surface film or corrosion; and to ensure that electronics remain correctly calibrated.

COMMENTARY:

N/A

REFERENCES: 1) American Society for Testing and Materials. Standard specification for laboratory weights and precision mass standards, designation E 617-97 (Reapproved 2003). ASTM International, West Conshohocken, PA 19428-2959 (www.astm.org); 2) American Society for Testing and Materials. Standard method of testing top-loading, direct reading laboratory scales and balances. E 898-88 (Reapproved 2000). ASTM International, West Conshohocken, PA 19428-2959 (www.astm.org).


Are results of periodic accuracy checks recorded?

NOTE: Mass readings should be recorded in a log book. The deviations in log book readings should be no more than the precision required in the applications for which the balance is used. Acceptable ranges for readings must be specified.

COMMENTARY:

N/A


Are weights well-maintained (clean, in a covered container, not corroded) and are appropriate lifting or handling devices available?

NOTE: Weights must be well-maintained (covered when not in use, not corroded) and only be handled by devices that will not allow residual contaminants to remain on the masses. Certified masses will only meet their specifications if maintained in pristine condition.

COMMENTARY:

N/A


http://www.astm.org/


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PROCEDURES AND TEST SYSTEMS

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BLOOD TYPE, GROUP, AND/OR ANTIBODY SCREENS

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If immunohematology tests other than blood type, group, and antibody screen are performed, the Transfusion Medicine Checklist must be used.


Are package inserts for immunohematology typing sera in use available, and are typing sera used according to manufacturer's directions, or if alternative procedures are used, have they been evaluated to justify the changes?

COMMENTARY:

Package inserts for all immunohematology typing sera and reagent cells must be available, and these materials must be used according to manufacturer's directions. If the manufacturer's instructions are not followed, alternative procedures must have been evaluated to show that the reagents still perform as expected and intended. Testing methods used for ABO, Rh and antibody screening that are different from the manufacturer's instructions, are acceptable provided they are not prohibited by the manufacturer, have been demonstrated to be satisfactory, or have been approved by the U.S. Centers for Biologics Evaluation and Research (CBER).

REFERENCE: Food and Drug Administration. Guide to inspections of blood banks, Sep 1994.


Do records document acceptable reactivity and specificity of typing sera and reagent cells on each day of use, including a check against known positive and negative cells or antisera?

NOTE: 1. Records of specific reactivity checks for A cells, B cells, anti-A, and anti-B may be omitted when forward and reverse grouping results consistently agree

2. Each cell used for antibody detection must be checked each day of use for reactivity of at least one antigen using antisera of 1+ to 3+ avidity

3. Anti-D typing reagents must be checked each day of use

COMMENTARY:



Typing sera must be checked for reactivity and specificity on each day of use against known positive and negative cells.

REFERENCE: Department of Health and Human Services, Centers for Medicare and Medicaid Services. Clinical laboratory improvement amendments of 1988; final rule. Fed Register. 2003(Jan 24):7171 [42CFR493.1271].


Are criteria for agglutination and/or hemolysis defined?

COMMENTARY:

Criteria must be defined in the procedure manual to provide uniformity of interpretation of positive and negative agglutination and hemolysis results.


Are observations of all test results recorded properly at the time done?

COMMENTARY:

Test results must be recorded at the time done in order to reduce the risk of transcription errors from delayed recording.


Are appropriate control(s) used for anti-D testing?

NOTE: High protein anti-D reagents require concurrent testing of an inert preparation of the manufacturer's diluent. Monoclonal anti-D reagents do not ordinarily require a separate reagent control. Incorrect assignment of a D-positive phenotype can be ruled out by observing negative reactions in any tube containing red cells and patient serum, or, alternatively, patient cells suspended in 5% bovine albumin.

COMMENTARY:

N/A



**NEW** 04/06/2006


Are ABO, Rh, and antibody screen test results compared against the same tests performed previously to detect discrepancies and identify patients requiring specially selected units?

NOTE: Comparison of records of previous ABO and Rh typing are an essential step in compatibility testing. Available laboratory records for each patient must be routinely searched whenever compatibility testing is performed. If no record of the patient’s blood type is available from previous determination(s), the transfusion service should be aware that there is an increased probability of an incorrect blood type assignment and, consequently, of a hemolytic transfusion reaction.

COMMENTARY:

N/A

**NEW** 04/06/2006


Are records available that document investigation and reconciliation of all cases in which ABO and Rh typing results were not in accord with the patient's historical record?

NOTE: Available laboratory records for each patient must be routinely searched whenever compatibility testing is performed. Quality management records must include an investigation of all cases in which the ABO or Rh typing was not in accordance with the patient's laboratory historical record.

COMMENTARY:

N/A

**NEW** 04/06/2006


When a direct antiglobulin test is ordered by a patient's physician, does the test system allow detection of RBC-bound complement as well as IgG?

NOTE: This ensures detection of patients with paroxysmal cold hemoglobinuria, cold hemagglutinin disease (CHAD), warm autoimmune hemolytic anemia, and drug-induced hemolytic anemia. For the purpose of diagnosing hemolytic disease of the newborn, use of anti-C3’d is not required.



Patients with cold hemagglutinin disease, anemia related to some immune complex-mediated hemolytic states (e.g., drug-induced immune complex hemolytic anemia), and up to 15% of patients with warm antibody autoimmune hemolytic anemia may have a positive direct antiglobulin test from complement coating of their red cells, without detectable IgG on the red cells.

COMMENTARY:

N/A

REFERENCES: 1) Sokol RJ, et al. Autoimmune haemolysis: an 18-year study of 865 cases referred to a regional transfusion centre. Brit Med J. 1981;282:2023-2027; 2) Packman CH, Leddy JP, Cryopathic hemolytic syndromes. In: Beutler E, et al, eds. William's Hematology, 5th ed. New York: McGraw-Hill, 1995:685-691; 3) Vengelen-Tyler V, ed. American Association of Blood Banks Technical Manual, 13th ed. Bethesda, MD: AABB Press, 1999:259-262.


When performing an antiglobulin test with anti-IgG or polyspecific antiglobulin reagents, are IgG-coated red blood cells used in all negative antiglobulin tests?

NOTE: IgG-coated red blood cells must be used to confirm all negative antiglobulin tests when the antiglobulin reagent used for testing has anti-IgG reactivity. Tests found negative by tube methodology must be checked with the addition of appropriate check cells. If a licensed system is used that does not require the use of IgG- coated cells, an appropriate quality control system must be followed, as recommended by the manufacturer.

COMMENTARY:

N/A


When performing an antiglobulin test with anti-C3 antiglobulin reagents, are C3-coated red blood cells used in all negative antiglobulin tests?

NOTE: Complement-coated red blood cells should be used to confirm all negative antiglobulin tests when the antiglobulin reagent used for testing has anti-C3 reactivity. Tests found negative by tube methodology should be checked with the addition of appropriate check cells. If a licensed system is used that does not require the use of C3-coated cells, an appropriate quality control system must be followed, as recommended by the manufacturer.

COMMENTARY:



N/A

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SYPHILIS SEROLOGY

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If antigen is delivered by needles, is the volume of delivery checked under each of the following circumstances?

1. Each time a new needle is used2. When control patterns cannot be reproduced3. When the antigen drop does not fall cleanly from the tip

NOTE: The Centers for Medicare and Medicaid Services (CMS) has adopted the following Centers for Disease Control (CDC) recommendations for checking needles used for the RPR and syphilis-related cardiolipin-based tests [e.g., toluidine red unheated serum test (TRUST)]. RPR needles must be checked under each of the following circumstances:

1. Each time a new needle is used2. When control patterns cannot be reproduced3. When a drop of antigen does not drop cleanly from the tip of the needle

COMMENTARY:

N/A


Is a negative control, plus positive serum controls of known titer or controls of graded reactivity run each day of patient testing?

NOTE: A negative control plus positive serum controls of known titer must be run each day of patient testing. If the laboratory reports graded patient results, then graded controls must be run.

COMMENTARY:

N/A

REFERENCE: Department of Health and Human Services, Centers for Medicare and Medicaid Services. Clinical laboratory improvement amendments of 1988; final rule. Fed Register. 2003(Jan 24):3708 [42CFR493.1256(d)(3)(iii)].



**REVISED** 04/06/2006


Are new reagent lots of antigen for VDRL, RPR, TRUST (toluidine red unheated serum test), and USR (unheated serum reagin) tests checked in parallel with reference reagents to verify that they are of standard reactivity?

NOTE: New reagent lots of antigen for VDRL, RPR, TRUST, and USR tests must be checked in parallel with reference reagents to verify that they are of standard reactivity. Because the ability of a reagent to detect specimens with low-grade reactivity is necessary for the diagnosis of primary syphilis, serum samples of graded reactivity, including those with weak reactivity, must be used. Reactive serum diluted with nonreactive serum to produce various degrees of reactivity may also be used. Roughness of an antigen can best be detected using fresh serum samples obtained from persons without syphilis. Prior to testing patient samples with a new reagent lot, parallel testing must be performed by using specimens of graded reactivity, including minimum/weakly reactive samples (for example, a reactive, a weakly reactive and a negative specimen). If one set of parallel tests shows borderline results, a second set of parallel tests should be performed.

COMMENTARY:

N/A

REFERENCE: Kennedy EJ, et al. Quality Control. In, SA Larsen et al (eds). A manual of tests for syphilis, 9th ed. Washington, DC: American Public Health Association, 1998; chap 4.

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PERSONNEL

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Does the person in charge of the technical operations in immunology and syphilis serology have education and experience equivalent to an MT (ASCP) and at least 4 years experience (one of which is in immunology and syphilis serology) under a qualified director?

COMMENTARY:

N/A



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PHYSICAL FACILITIES

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Sufficient space and utilities need to be provided for the overall workload of the immunology/syphilis serology section, and to meet all safety requirements.


Is there adequate space for administrative functions?

COMMENTARY:

N/A


Is there adequate space for clerical work?

COMMENTARY:

N/A


Is there adequate space for technical work (bench space)?

COMMENTARY:

N/A


Is there adequate space for instruments?

COMMENTARY:

N/A




Is there adequate space for shelf storage?

COMMENTARY:

N/A


Is there adequate refrigerator/freezer storage space?

COMMENTARY:

N/A


Is the available space efficiently utilized?

COMMENTARY:

N/A


Is sufficient space available so that there is no compromise of the quality of work, (including quality control activities) or safety of personnel?

COMMENTARY:

N/A

REFERENCE: Elin RJ, Gersch SM. Considerations for the design of a new laboratory. Am J Clin Pathol. 1986;85:61-66.


Are floors and benches clean, free of clutter, and well-maintained?

COMMENTARY:



N/A


Are water taps, sinks, and drains adequate?

COMMENTARY:

N/A


Are electrical outlets adequate?

COMMENTARY:

N/A


Is lighting adequate?

NOTE: Direct sunlight should be avoided because of its extreme variability and the need for low light levels necessary to observe various computer consoles, etc. Lighting control should be sectionalized so general levels of illumination can be controlled in areas of the room if desired.

COMMENTARY:

N/A


Is ventilation adequate?

COMMENTARY:

N/A


Is temperature/humidity control adequate?



COMMENTARY:

N/A


Is gas and suction adequate?

COMMENTARY:

N/A


Are telephones conveniently located, and are calls easily transferred?

COMMENTARY:

N/A
